Immune cells can be potent and specific “living drugs”. Immune cells have the potential to target tumor cells while sparing normal tissues; several clinical observations indicate that they can have major anti-cancer activity. Thus, in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT), T-cell-mediated graft-versus-host disease (GvHD) (Weiden, P L et al., N. Engl. J. Med. 1979; 300(19):1068-1073; Appelbaum, F R Nature, 2001; 411(6835):385-389; Porter, D L et al., N. Engl. J. Med. 1994; 330(2):100-106; Kolb, H J et al. Blood. 1995; 86(5):2041-2050; Slavin, S. et al., Blood. 1996; 87(6):2195-2204), and donor natural killer (NK) cell alloreactivity (Ruggeri L, et al. Science. 2002; 295(5562):2097-2100; Giebel S, et al. Blood. 2003; 102(3):814-819; Cooley S, et al. Blood. 2010; 116(14):2411-2419) are inversely related to leukemia recurrence. Besides the HSCT context, administration of antibodies that release T cells from inhibitory signals (Sharma P, et al., Nat Rev Cancer. 2011; 11(11):805-812; Pardoll D M., Nat Rev Cancer. 2012; 12(4):252-264), or bridge them to tumor cells (Topp M S, et al. J. Clin. Oncol. 2011; 29(18):2493-2498) produced major clinical responses in patients with either solid tumors or leukemia. Finally, infusion of genetically-modified autologous T lymphocytes induced complete and durable remission in patients with refractory leukemia and lymphoma (Maude S L, et al. N Engl J Med. 2014; 371(16):1507-1517).
Nevertheless, there is a significant need for improving immune cell therapy by broadening its applicability and enhancing its efficacy.